An extended motif in the SARS-CoV-2 spike modulates binding and release of host coatomer in retrograde trafficking.

Autor: Dey D; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA., Singh S; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA., Khan S; Protein and Crystallography Facility, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.; Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, USA., Martin M; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.; University of Pittsburgh Kenneth P. Dietrich School of Arts and Sciences, Pittsburgh, PA, USA., Schnicker NJ; Protein and Crystallography Facility, Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Gakhar L; Protein and Crystallography Facility, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.; Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.; PAQ Therapeutics, Cambridge, MA, USA., Pierce BG; W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA., Hasan SS; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA. sshasan@som.umaryland.edu.; University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland Medical Center, Baltimore, MD, USA. sshasan@som.umaryland.edu.; Center for Biomolecular Therapeutics, University of Maryland School of Medicine, Rockville, MD, USA. sshasan@som.umaryland.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2022 Feb 08; Vol. 5 (1), pp. 115. Date of Electronic Publication: 2022 Feb 08.
DOI: 10.1038/s42003-022-03063-y
Abstrakt: β-Coronaviruses such as SARS-CoV-2 hijack coatomer protein-I (COPI) for spike protein retrograde trafficking to the progeny assembly site in endoplasmic reticulum-Golgi intermediate compartment (ERGIC). However, limited residue-level details are available into how the spike interacts with COPI. Here we identify an extended COPI binding motif in the spike that encompasses the canonical K-x-H dibasic sequence. This motif demonstrates selectivity for αCOPI subunit. Guided by an in silico analysis of dibasic motifs in the human proteome, we employ mutagenesis and binding assays to show that the spike motif terminal residues are critical modulators of complex dissociation, which is essential for spike release in ERGIC. αCOPI residues critical for spike motif binding are elucidated by mutagenesis and crystallography and found to be conserved in the zoonotic reservoirs, bats, pangolins, camels, and in humans. Collectively, our investigation on the spike motif identifies key COPI binding determinants with implications for retrograde trafficking.
(© 2022. The Author(s).)
Databáze: MEDLINE
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